We have at least 20 healthy, aged male and female rhesus monkeys (20 yr or older) at the Oregon Regional Primate Research Center. It is possible to obtain multiple biopsies of predominately red or white muscle from these monkeys without interfering with their mobility. The lipofuscin content (age-related fluorescent pigment) has generally been considered the best single measure of aging currently available; however, no data on primate skeletal muscle are available. We are measuring the lipofuscin content by fluorescence microscopy and the number and ratios of type I, type IIa and type IIb fiber types of adult and senescent rhesus muscle samples histochemically (Ca2 ion and Mg2 ion ATPase at pH 9.4 and succinic dehydrogenase). We are also investigating the basal activity and kinetics of the enzymes synthesizing (adenylate and guanylate cyclases) and degrading (phosphodiesterases) the cyclic nucleotides of adult and aged monkey muscle. The sensitivity of these enzymes to effector molecules such as ATP, GTP, cGMP, and Ca2 ion is being studied since enzymes in vivo rarely, if ever, operate at maximum efficiency; their activity depends on the balance of activators, inhibitors, coenzymes, substrates, products, hormones, and other factors in the environment such as pH and ionic concentrations. To date the data indicates that the activities of both adenylate and guanylate cyclase enzymes are greater in aged than in young adult monkeys. The production of prostaglandins (PGE2, PGF2 alpha, PGD2, thromboxane B2, and 6-keto PGF1 alpha is also being measured in young and old skeletal muscle under different physiological conditions. Preliminary results on cAMP-PDE and cGMP-phosphodiesterase suggest that these enzymes may also be more active in the older muscle. The total activity and the relative amounts of type I and II cAMP-dependent and cGMP-dependent protein kinases will eventually be examined. We will not have time to finish these investigations in the proposed 3-year period.